Skip to main content

Advertisement

Log in

Osteoporosis Caused by Systemic Mastocytosis: Prevalence in a Cohort of 8392 Patients with Osteoporosis

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Indolent systemic mastocytosis (ISM) is a group of heterogenous diseases characterized by abnormal accumulation of mast cells in at least one organ. ISM can be a cause of osteoporosis. The aim of this study is to determine the prevalence, and the prognosis of ISM in a cohort of patients with osteoporosis. In this monocentric and retrospective study, patients with osteoporosis who did not receive a bone biopsy (cohort 1) and patients that subsequently received a diagnostic bone biopsy for differential diagnosis (cohort 2) are compared with patients who are diagnosed with ISM (cohort 3). A total of 8392 patients are diagnosed with osteoporosis. Out of these patients 1374 underwent a diagnostic bone biopsy resulting in 43 patients with ISM. These figures indicate that ISM is diagnosed in 0.5% of patients with osteoporosis and in 3.1% (men 5.8%) of patients who underwent bone biopsies. Patients with ISM sustained significantly more vertebral fractures in comparison to patients in cohort 2 (4.4 ± 3.6 versus 2.4 ± 2.5 vertebral fractures, p < 0.001) and women were significantly younger compared to cohort 2 (57.3 ± 12 versus 63.6 ± 12 years, p < 0.05). Only 33% showed an involvement of the skin (urticaria pigmentosa). ISM is a rare cause of osteoporosis (0.5%). However, in a subgroup of rather young male patients with osteoporosis the prevalence is more than 5%. Thus, ISM should be considered in premenopausal women and men presenting with vertebral fractures even if urticaria pigmentosa is not present.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Valent P (2013) Mastocytosis: a paradigmatic example of a rare disease with complex biology and pathology. Am J Cancer Res 3(2):159–172

    PubMed  PubMed Central  Google Scholar 

  2. Cohen SS, Skovbo S, Vestergaard H, Kristensen T, Møller M, Bindslev-Jensen C, Fryzek JP, Broesby-Olsen S (2014) Epidemiology of systemic mastocytosis in Denmark. Br J Haematol 166(4):521–528. https://doi.org/10.1111/bjh.12916

    Article  PubMed  Google Scholar 

  3. Valent P, Akin C, Gleixner K, Sperr W, Reiter A, Arock M, Triggiani M (2019) Multidisciplinary challenges in mastocytosis and how to address with personalized medicine approache. Int J Mol Sci 20:297. https://doi.org/10.3390/ijms20122976

    Article  CAS  Google Scholar 

  4. Meyer HJ, Pönisch W, Monecke A, Gundermann P, Surov A (2021) Bone mineral density in patients with systemic mastocytosis: correlations withclinical and histopathological features. Clin Exp Rheumatol 39(1):52–57

    PubMed  Google Scholar 

  5. Riffel P, Schwaab J, Lutz C, Naumann N, Metzgeroth G, Fabarius A, Schoenberg SO, Hofmann WK, Valent P, Reiter A, Jawhar M (2020) An increased bone mineral density is an adverse prognostic factor in patientswith systemic mastocytosis. J Cancer Res Clin Oncol 146(4):945–951. https://doi.org/10.1007/s00432-019-03119-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Orsolini G, Viapiana O, Rossini M, Bonifacio M, Zanotti R (2018) Bone disease in mastocytosis. Immunol Allergy Clin N Am 38(3):443–454. https://doi.org/10.1016/j.iac.2018.04.013

    Article  Google Scholar 

  7. Degboé Y, Eischen M, Apoil PA, Mailhol C, Dubreuil P, Hermine O, Paul C, Bulai Livideanu C, Laroche M (2019) Higher prevalence of vertebral fractures in systemic mastocytosis, but not incutaneous mastocytosis and idiopathic mast cell activation syndrome. Osteoporos Int 30(6):1235–1241. https://doi.org/10.1007/s00198-019-04918-7

    Article  CAS  PubMed  Google Scholar 

  8. Acosta-Mérida Á, Ojeda-Bruno S (2019) Multiple vertebral fractures as the first manifestation of systemic mastocytosis. Osteoporos Int 30(5):1121–1124. https://doi.org/10.1007/s00198-019-04897-9

    Article  PubMed  Google Scholar 

  9. Bouvard B, Pascaretti-Grizon F, Legrand E, Lavigne C, Audran M, Chappard D (2020) Bone lesions in systemic mastocytosis: bone histomorphometry and histopathological mechanisms. Morphologie 104(345):97–108. https://doi.org/10.1016/j.morpho.2020.01.004

    Article  CAS  PubMed  Google Scholar 

  10. Rabenhorst A, Christopeit B, Leja S, Gerbaulet A, Kleiner S, Förster A, Raap U, Wickenhauser C, Hartmann K (2013) Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis. J Allergy Clin Immunol 132(5):1234–1237. https://doi.org/10.1016/j.jaci.2013.06.019

    Article  CAS  PubMed  Google Scholar 

  11. Seitz S, Barvencik F, Koehne T, Priemel M, Pogoda P, Semler J, Minne H, Pfeiffer M, Zustin J, Püschel K, Eulenburg C, Schinke T, Amling M (2013) Increased osteoblast and osteoclast indices in individuals with systemic mastocytosis. Osteoporos Int 24(8):2325–2334. https://doi.org/10.1007/s00198-013-2305

    Article  CAS  PubMed  Google Scholar 

  12. Rossini M, Zanotti R, Orsolini G, Tripi G, Viapiana O, Idolazzi L, Zamò A, Bonadonna P, Kunnathully V, Adami S, Gatti D (2016) Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis. Osteoporos Int 27(8):2411–2421. https://doi.org/10.1007/s00198-016-3539-1

    Article  CAS  PubMed  Google Scholar 

  13. Laroche M, Livideanu C, Paul C, Cantagrel A (2011) Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis. Am J Med 124(8):776–778. https://doi.org/10.1016/j.amjmed.2011.02.038

    Article  CAS  PubMed  Google Scholar 

  14. van der Veer E, van der Goot W, de Monchy JG, Kluin-Nelemans HC, van Doormaal JJ (2012) High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis. Allergy 67(3):431–438. https://doi.org/10.1111/j.1398-9995.2011.02780

    Article  PubMed  Google Scholar 

  15. Rossini M, Zanotti R, Bonadonna P, Artuso A, Caruso B, Schena D, Vecchiato D, Bonifacio M, Viapiana O, Gatti D, Senna G, Riccio A, Passalacqua G, Pizzolo G, Adami S (2011) Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone 49(4):880–885. https://doi.org/10.1016/j.bone.2011.07.004

    Article  PubMed  Google Scholar 

  16. Greene LW, Asadipooya K, Corradi PF, Akin C (2016) Endocrine manifestations of systemic mastocytosis in bone. Rev Endocr Metab Disord 17(3):419–431. https://doi.org/10.1007/s11154-016-9362-3

    Article  CAS  PubMed  Google Scholar 

  17. van der Veer E, Arends S, van der Hoek S, Versluijs JB, de Monchy JGR, Oude Elberink JNG, van Doormaal JJ (2014) Predictors of new fragility fractures after diagnosis of indolent systemic mastocytosis. J Allergy Clin Immunol 134(6):1413–1421. https://doi.org/10.1016/j.jaci.2014.05.003

    Article  PubMed  Google Scholar 

  18. Zanotti R, Lombardo C, Passalacqua G, Caimmi C, Bonifacio M, De Matteis G, Perbellini O, Rossini M, Schena D, Busa M, Marcotulli MC, Bilò MB, Franchini M, Marchi G, Simioni L, Bonadonna P (2015) Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels. J Allergy Clin Immunol 136(1):135–139. https://doi.org/10.1016/j.jaci.2014.11.035

    Article  CAS  PubMed  Google Scholar 

  19. Degboé Y, Eischen M, Nigon D, Apoil PA, Mailhol C, Tournier E, Laurent C, Hanssens K, Hermine O, Paul C, Laroche M, Bulai-Livideanu C (2017) Prevalence and risk factors for fragility fracture in systemic mastocytosis. Bone 105:219–225. https://doi.org/10.1016/j.bone.2017.09.005

    Article  PubMed  Google Scholar 

  20. Rossini M, Zanotti R, Viapiana O, Tripi G, Orsolini G, Idolazzi L, Bonadonna P, Schena D, Escribano L, Adami S, Gatti D (2014) Bone involvement and osteoporosis in mastocytosis. Immunol Allergy Clin N Am 34(2):383–396. https://doi.org/10.1016/j.iac.2014.01.011

    Article  Google Scholar 

  21. Barete S, Assous N, de Gennes C, Grandpeix C, Feger F, Palmerini F, Dubreuil P, Arock M, Roux C, Launay JM, Fraitag S, Canioni D, Billemont B, Suarez F, Lanternier F, Lortholary O, Hermine O, Francès C (2010) Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis 69(10):1838–4. https://doi.org/10.1136/ard.2009.124511

    Article  CAS  PubMed  Google Scholar 

  22. Escribano L, Alvarez-Twose I, Sánchez-Muñoz L, Garcia-Montero A, Núñez R, Almeida J, Jara-Acevedo M, Teodósio C, García-Cosío M, Bellas C, Orfao A (2009) Prognosis in adult indolent systemic mastocytosis: a long-term study of the Spanish Network on Mastocytosis in a series of 145 patients. J Allergy Clin Immunol 124(3):514–521. https://doi.org/10.1016/j.jaci.2009.05.003

    Article  PubMed  Google Scholar 

  23. Delling G, Ritzel H, Werner M (2001) Histological characteristics and prevalence of secondary osteoporosis in systemic mastocytosis. A retrospective analysis of 158 cases. Pathologe 22(2):132–40. https://doi.org/10.1007/s002920000439

    Article  CAS  PubMed  Google Scholar 

  24. Arock M, Sotlar K, Akin C, Broesby-Olsen S, Hoermann G, Escribano L, Kristensen TK, Kluin-Nelemans HC, Hermine O, Dubreuil P, Sperr WR, Hartmann K, Gotlib J, Cross NC, Haferlach T, Garcia-Montero A, Orfao A, Schwaab J, Triggiani M, Horny HP, Metcalfe DD, Reiter A, Valent P (2015) KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia 29(6):1223–1232. https://doi.org/10.1038/leu.2015.24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Valent P, Escribano L, Broesby-Olsen S, Hartmann K, Grattan C, Brockow K, Niedoszytko M, Nedoszytko B, Oude Elberink JN, Kristensen T, Butterfield JH, Triggiani M, Alvarez-Twose I, Reiter A, Sperr WR, Sotlar K, Yavuz S, Kluin-Nelemans HC, Hermine O, Radia D, van Doormaal JJ, Gotlib J, Orfao A, Siebenhaar F, Schwartz LB, Castells M, Maurer M, Horny HP, Akin C, Metcalfe DD, Arock M, European Competence Network on Mastocytosis (2014) Proposed diagnostic algorithm for patients with suspected mastocytosis: a proposal of the European Competence Network on Mastocytosis. Allergy 69(10):1267–74. https://doi.org/10.1111/all.12436

    Article  CAS  PubMed  Google Scholar 

  26. Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, Sotlar K, Sperr W, Escribano L, George T, Kluin-Nelemans H, Ustun C, Triggiani M, Brockow K, Gotlib J, Orfao A, Schwartz L, Broesby-Olsen S, Bindslev-Jensen C, Kovanen P, Galli S, Austen F, Arber D, Horny H, Arock M, Metcalfe D (2017) Advances in the classification and treatment of mastocytosis: current status and outlook toward the future. Cancer Res 77(6):1261–1270. https://doi.org/10.1158/0008-5472.CAN-16-2234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rossini M, Zanotti R, Viapiana O, Tripi G, Idolazzi L, Biondan M, Orsolini G, Bonadonna P, Adami S, Gatti D (2014) Zoledronic acid in osteoporosis secondary to mastocytosis. Am J Med 127(11):1127. https://doi.org/10.1016/j.amjmed.2014.06.015

    Article  CAS  PubMed  Google Scholar 

  28. Orsolini G, Gavioli I, Tripi G, Viapiana O, Gatti D, IdolazziL Zanotti R, Rossini M (2017) Denosumab for the treatment of mastocytosis-related osteoporosis: a case series. Calcif Tissue Int 100(6):595–598. https://doi.org/10.1007/s00223-017-0241-z

    Article  CAS  PubMed  Google Scholar 

  29. Wolf E, Röser K, Hahn M, Welkerling H, Delling G (1992) Enzyme and immunhistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: a new embedding method for routine application. Virchows Arch A Pathol Anat Histopathol 420:17–24. https://doi.org/10.1007/BF01605979

    Article  CAS  PubMed  Google Scholar 

  30. Arock M, Valent P (2010) Pathogenesis, classification and treatment of mastocytosis: state of the art in 2010 and future perspectives. Expert Rev Hematol 3(4):497–516. https://doi.org/10.1586/ehm.10.42

    Article  PubMed  Google Scholar 

  31. Nemeth K, Wilson TM, Ren J, Sabatino M, Stroncek DF, Krepuska M, Bai Y, Robey PG, Metcalfe DD, Mezey E (2015) Impaired function of bone marrow stromal cells in systemic mastocytosis. Stem Cell Res 15(1):42–53. https://doi.org/10.1016/j.scr.2015.04.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Artuso A, Caimmi C, Tripi G, Viapiana O, Bonifacio M, Idolazzi L, Gavioli I, Gatti D, Zanotti R, Rossini M (2017) Longitudinal evaluation of bone mineral density and bone metabolism markers in patients with indolent systemic mastocytosis without osteoporosis. Calcif Tissue Int 100(1):40–46. https://doi.org/10.1007/s00223-016-0198-3

    Article  CAS  PubMed  Google Scholar 

  33. Guillaume N, Desoutter J, Chandesris O, Merlusca L, Henry I, Georgin-Lavialle S, Barete S, Hirsch I, Bouredji D, Royer B, Gruson B, Lok C, Sevestre H, Mentaverri R, Brazier M, Meynier J, Hermine O, Marolleau JP, Kamel S, Pharm D, Damaj G (2013) Bone complications of mastocytosis. Am J Med 126(75):e1-75.e7. https://doi.org/10.1016/j.amjmed.2012.07.018

    Article  CAS  Google Scholar 

  34. Cardet JC, Akin C, Lee MJ (2013) Mastocytosis: update on pharmacotherapy and future directions. Expert Opin Pharmacother 14(15):2033–2045. https://doi.org/10.1517/14656566.2013.824424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Black DH, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356(18):1809–1822. https://doi.org/10.1056/NEJMoa067312

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors like to thank Prof. Dr. H. W. Minne, Dr. A.D. Lazarescu, Ch. Hinz, Dr. M. Fischer and B. Ide (Clinic DER FÜRSTENHOF, Bad Pyrmont, Germany) for supporting this study. In addition, authors are especially grateful to Mehrsheed Sinaki, M.D., M.S. (Mayo-Clinic, Rochester, MN, U.S.A.) for reading and reviewing the manuscript.

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

MG and HS wrote the manuscript. All authors contributed substantial parts to the elaboration of this study. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Martin Gehlen.

Ethics declarations

Conflict of interest

Martin Gehlen, Niels Schmidt, Michael Pfeifer, Subathira Balasingam, Michael Schwarz-Eywill, Anna Maier, Mathias Werner and Heide Siggelkow declare that they have no conflict of interest.

Ethical Approval

Retrospective study. For this type of study no formal informed consent is required (see above).

Informed Consent

According to the ethics committee responsible for our clinic, no formal informed consent is required for this type of retrospective study. Informed consent was obtained from each patient before undergoing a bone biopsy.

Human and Animal Rights

This retrospective trial does not include any treatment of humans or animals. Zoledronate was administrated according to the current German guidelines for treatment of osteoporosis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gehlen, M., Schmidt, N., Pfeifer, M. et al. Osteoporosis Caused by Systemic Mastocytosis: Prevalence in a Cohort of 8392 Patients with Osteoporosis. Calcif Tissue Int 109, 685–695 (2021). https://doi.org/10.1007/s00223-021-00887-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-021-00887-4

Keywords

Navigation